Infection in systemic lupus erythematosus: friend or foe?

Abstract

Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike. Keywords autoimmunity; infections; protective; systemic lupus erythematosus; vaccination Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and the mechanisms of the aberrant immune responses remain unclear. Several environmental factors have been implicated in the etiology of SLE. There is a concordance rate of 25% in monozygotic twins for SLE, which indicates a discordance rate of 70% contributed to by environmental factors [1].The possibility of a viral etiology was raised by the finding of virion-like tubuloreticular structures in endothelial cells and lymphocytes, and demonstration of increased concentration of type 1 interferon (IFN) in lupus patients [1]. Many viruses have been implicated in the etiology of SLE, which includes the Epstein-Barr virus (EBV), transfusion-transmitted virus (tissue transplant virus or Torque tenovirus), retroviruses, paramyxovirus, cytomegalovirus (CMV), parvovirus B19 and corona virus (Table 1). EBV, retroviruses and parvovirus B19 may play a role in the pathogenesis of SLE, when compared with other viruses such as CMV, transfusion transmitted virus, type C oncorna virus and measles virus which play a minor role. Immunodeficiency, such as C4 or C1q deficiency, may predispose to both lupus and infection without the two being directly linked. Infectious agents may induce autoimmune disease by several mechanisms. Structural & functional molecular mimicryMolecular mimicry may be structural or functional. Structural molecular mimicry occurs when a viral peptide has an amino acid sequence similar or identical to an amino acid sequence of a self peptide, resulting in cross-reactive T-cell and B-cell responses. A potentially autoreactive NIH Public Access Author ManuscriptInt J Clin Rheumtol. Author manuscript; available in PMC 2010 December 1. Published in final edited form as:Int J Clin Rheumtol. Stimulation of pathogen recognition receptorsExogenous stimuli are products of bacteria and viruses and have been termed pathogenassociated molecular patterns (PAMPs) [6]. Dendritic cells recognize PAMPs using pathogen recognition receptors, such as Toll-like receptors (TLRs). Necrotic debris from the cell death pathways, bacterial lipopolysaccharide, viral RNA and viral DNA act...

The Relationship of Systemic Lupus Erythematosus and Helicobacter Pylori

“…In another study anti-H. Pylori antibodies were found at low titers in SLE patients compared to other autoimmune diseases [10]. In the most recent study, it was concluded that there is generally a negative relationship of various infectious agents, including H. Pylori, in the development of SLE [11]. In an animal study, H. Pylori exposed to urease enzyme was found to lead to the formation of anti-ssDNA antibodies [12].…”

Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

“…Our recent finding that IgG4 autoAbs in FS cross-react with an LJM11 sand fly antigen (13) suggests that the development of IgG4 autoAbs in patients may be linked to exposure to an environmental antigen. The studies of the association of environmental factors, such as infectious agents, with the development of autoimmune diseases have a long history (15, 17–19, 31–34). However, the studies of non-infectious antigens and their association with the development of autoimmune diseases are scarce.…”

“…Given that anti-LJM11 Abs cross-react to autoantigen Dsg1 (13, 36) strongly suggests the existence of a “cross-reactive” epitope(s) on both LJM11 and Dsg1. Since exposure to exogenous antigens may induce the autoimmune response to ”cross-reactive” autoantigens in autoimmune diseases (33, 34, 37–39), we hypothesize that the immune response directed against this “cross-reactive” epitope(s) subsequently initiates the generation of IgG4 autoAbs in FS susceptible individuals.…”

Helicobacter pylori as a trigger and aggravating factor in rheumatoid arthritis and other rheumatic diseases

“…Хотя иммунные нарушения, возникающие вследст-вие инфекции, могут играть определенную роль в формиро-вании свойственных СКВ аутоантител, тем не менее нет четких данных о том, что при этом заболевании инфициро-ванность H. pylori и наличие более патогенных штаммов этого микроорганизма выше, чем в популяции [42,43]. Так, американские ученые A.Н.…”